Production of 5-Membered and 6-Membered Cyclic Esters of Polyols

ABSTRACT

Described herein are improved methods for the preparation of 5- and 6-membered cyclic mono and diesters of sugar alcohols and anhydrosugar alcohols by reaction with an organic acid RCOOH over a solid acidic substrate. The process is adaptable to a continuous process for simultaneously making and separating the cyclic esters from the sugar alcohols and anhydrosugar alcohols under mild conditions using the solid acid substrate as both the catalyst and a chromatographic bed for separation. The reactions are performed at mild temperatures of 70° C. to 100° C. and the formation of the cyclic esters is nearly quantitative. Also described is a method for making 5- and 6-membered cyclic mono and diesters of sugar alcohols and anhydrosugar alcohols using microwave irradiation in the presence of the organic acid.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.12/993,143, which is a 35 U.S.C. §371 national phase entry ofInternational Application No. PCT/US2009/045383 filed May 28, 2009,which claims priority to U.S. provisional patent application No.61/056,678 filed May 28, 2008, each of the contents of which isincorporated herein by reference in its entirety.

FIELD OF INVENTION

This application pertains to an improved method for the preparation of5- and 6-membered cyclic esters of 5 and 6 carbon polyols. Inparticular, the application relates to a continuous process for makingand separation of cyclic esters from sugar alcohols and anhydrosugaralcohols under mild conditions using a solid acid substrate as acatalyst.

BACKGROUND

Cyclic esters of sugar alcohols such as D-sorbitol and D-mannitol havewide commercial utility as a lubricant or hydraulic oil as well asnon-ionic emulsifying agents, power train and heat transfer media,dielectrics, process oils and solvents. These cyclic esters areenvironmentally friendly, biodegradable oils and lubricants. Simple andcost effective methods of producing five- and six-membered cyclic estersfrom sugar alcohols and their dehydration products are desired.

SUMMARY

The present teaching provides a simple and cost effective method for thepreparation and separation of 5- and 6-membered cyclic esters of sugaralcohols and their monoanhydro and dianhydro derivatives by reactionwith an organic acid on a solid acid catalyst bed, which is adaptablefor use in a continuous flow process for simultaneous synthesis andseparation of the esters from the starting sugar alcohols or theirmonoanhydro and dianhydro derivatives.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a chromatographic profile for simultaneous synthesis ofcyclic mono and diesters from sorbitol and acetic acid andchromatographic separation from sorbitol on an acidic resin that acts asa catalyst and chromatographic separation media.

FIG. 2 shows a chromatographic profile for simultaneous synthesis ofcyclic mono and diesters from isosorbide and acetic acid andchromatographic separation from isosorbide on an acidic resin acts as acatalyst and chromatographic separation media.

FIG. 3 shows an HPLC analysis to identify mono and diesters made bymicrowave facilitated reaction of acetic acid and isosorbide.

FIG. 4 schematically depicts a continuous simulated moving bedchromatographic process for the preparation of cyclic esters from sugaralcohols or their monoanhydro or dianhydro derivatives.

DETAILED DESCRIPTION

This disclosure relates to a chromatographic process to synthesizecyclic esters of 5 and 6 carbon sugar alcohols and their monanhydro anddianhydro derivatives in accordance with the following reaction scheme:

where R and R′ are independently hydrogen, alkyl, aryl, vinyl,alkenylallyl. Isosorbide, which is the starting material depicted aboveis an end product of the progresseive acid catalyzed dehydration ofsorbitol to first the monoanhdyo then the dianhydro sugar alcoholaccording to the reaction scheme below:

Because acid catalyzes the dehydration as well as the ultimateesterification with the added organic acid, the starting materialsuseful in the present teaching can be any polyol that undergoes acidcatalyzed dehydration. Typical polyol starting materials include sugaralcohols, monoanhydrosugar and dianhydrosugar alcohols, dianhydrosugarmonoesters or a mixture of such alcohols. Accordingly, the term “polyol”is used generically herein to be inclusive of the aforementioned subgenus of compounds. Generally, the preferred starting materials includearabinitol, ribitol, sorbitol, mannitol, isosorbide, sorbitan,isoiodide, isomannide, galactitol and iditol. Pentitols such as xylitolcan also be used. Isosorbide, which is the dianhydro sugar alcoholderivative of sorbitol, is depicted in the reaction above and is aparticularly preferred starting material because it is readily availableor easily made from the dehydration of sorbitol. Sorbitan which is themonanhydro sugar alcohol derivative of sorbitol is also a desirablestarting material, but the reaction works with sorbitol and otherpolyols as well. The starting materials may be “crude”, i.e., containedin an impure state as mixtures with one another or with minornon-reactive impurities.

In a typical practice, the reaction is carried out on a solid acidcatalyst. Examples of such solid acids include acidic resins such asAmberlyst 35, Amberlyst 15, Amberlyst 36, Amberlyst 70, and Amberlyst131 from Rohm and Haas; Purolite CT-145, Lewatit S2328, Lewatit K2431,Lewatit S2568, Lewatit K2629 from Bayer Company; and Dianion SK104,PK228, RCP160 and Relite RAD/F from Mitsubishi Chemical America, Inc. Indiffering embodiments, the solid acid catalyst may be a weak or a strongacid catalyst. In other practices, the solid acid catalyst can be acidgroups associated with non-resin substrates such as clays, zeolites,alumina, etc. Examples of such solid acids include zeolites such as CBV3024, 5534G, T-2665, T-4480, and CS331-3. The solid acid catalyst may bea calcined zeolite.

One process involves exposure of a mono or dianhydrosugar alcohol orsugar alcohol to an acid catalyst in the presence of an organic acidRCOOH, at a temperature and pressure for a period of time (dependent onreaction conditions) sufficient to provide mono and dianhydrosugaresters, which are mono cyclic or dicyclic respectively. Anotherindependent but related process involves microwave irradiation of thepolyol in the presence of the organic acid including but not limited toa sugar alcohol and an anhydrosugar alcohol to provide cyclic esters.

The reactions conditions are preferably relatively mild. The reaction iscarried out at a temperature from about 70° C. to about 100° C. atambient pressure. More typically the reaction temperature is about 80°C. to 100° C. and in exemplary practices the reaction temperature isabout 85° C. When the acid catalyst is in the form of a column bed, thecolumn can be equilibrated with the desired organic acid (RCOOH) and thereaction commenced by heating the bed to the desired temperature andloading the sugar alcohol or anhydro sugar alcohol to one end of thecolumn. The column may be eluted using the same organic acid as theeluent. The passage of the reactants over the column bed affects asimultaneous synthesis of the polyol estesr and chromatographicseparation of the esters from unreacted sugar alcohol or anhydrosugaralcohol As shown in FIG. 1, unreacted sorbitol tends to elute after thepeak of isosorbide esters. As shown best in FIG. 2, unreacted isorobidetends to elute just before the peak of isosorbide esters Followingseparation of the product from the reaction mixture, furtherpurification of the different esters can be done using procedures suchas recrystallization or distillation or other chemical purificationtechniques well known in the art.

The use of a column(s) in the synthetic and purification processesenables a continuous flow of a heated anhydrosugar alcohol or sugaralcohol solution, thereby decreasing the amount of by-product formation,polymerization, and resin deactivation. The use of solid phase catalyststo chromatographically synthesize and separate isosorbide esters andcyclic esters of polyols is novel.

When the starting source is a sugar alcohol material, the intermediatecompounds of monoanhydrosugar alcohol and dianhydrosugar alcohol may beobtained and recycled to give the desired ester products. Another uniqueaspect of this teaching is that any fraction containing unreacted sugaralcohol or anhydrosugar alcohol can be allowed to react again byrecycling onto the column. Mixed fractions can be rechromatographed.This process differs from prior art in that sorbitol containingfractions may be recycled until pure isosorbide esters are obtained. Asopposed to the process of the present teaching, recycling of startingmaterial heretofore has not been an option and longer reaction timeshave led to polymerization and tar formation. In the present teaching,the recycling of sugar alcohol and anhydrosugar alcohol containingmixtures (fractions) through a solid phase catalyst to generate andseparate cyclic esters of polyols and anhydro derivatives thereof doesnot produce the polymerization and tar formation as in the prior art.

The experimental design and set up of this process is not limited.Multiple chromatographic columns may be used when the feeding amount forthe chromatography is especially high. This aspect of this disclosure isadvantageous for industrial scale development. The material may flowthrough all of the resin columns or an elution stream may be insertedsuch that only a remainder of the stream passes through the completesystem. For example, several columns may be used specifically forsynthesis and a few columns used for separation and purification.Alternatively, the system may be but not limited to a jacketed glasscolumn, a falling film evaporator, a simulated moving bed, continuoussetup (CSEP), or a continuous flow pipe system.

A continuous chromatographic separation process using a simulatingmoving bed chromatographic device such as a CSEP system 100 isschematically illustrated in FIG. 4. The CSEP system 100 includes acontinuous stationary phase column bed 132 separated into a plurality(1-10) of segmented beds 32 on a carousel 132. The liquid moving phase,is loaded from one end of a first bed segment 32(1) and is passed fromthe opposite end of the first bed segment 32(1) to the top of the nextadjacent bed segment in the carousel 13(2) in fluid flow direction 115.At the same time the plurality of column bed segments 32 are rotated incarousel 132 in bed movement direction 135 that is counter current tothe fluid direction 115. Reactants are fed into segments of the columnat a first zone (depicted at segment 32(1)) for organic acids 110 and atsecond zone (depicted at segment 32(6) for sugar alcohols 120, each inthe fluid flow direction 115. It is understood in this depiction thatsugar alcohols 120 may include or be replaced by mono and/or anhydroderivatives thereof. The sugar alcohols 120 and organic acids 110contact each other over the catalytic bed 132 maximally in reactionzones of the carousel bed depicted as column segments 32(6) through32(9). The ester products 140 preferentially partition with thestationary phase of the column beds 32 relative to the sugar alcohols120, therefore, as the bed segments are rotated in bed flow direction135 the ester products 140 preferentially move with the bed segments andare eluted in a product elution zone depicted as segment 32(4). Incontrast, the sugar alcohols 120 relative to the esters 140preferentially partition with the liquid phase of organic acid 110 andtherefore flow toward an opposing portion of bed 132 and can bewithdrawn from an elution zone that is enriched with unreacted sugaralcohols 150 depicted at segment 32(10) of column bed 132. In anoptional embodiment, the eluted sugar alcohols 150 can be combined withthe input sugar alcohols 120 to maximize reactant utilization.Optionally, a wash elution zone may be introduced between the elutionzone at column segment 32(1) and the reload zone at column segment 32(1)to regenerate the column bed, in which case an additional wash elutionport would be configured to collect the waste product In any case, whenhen the overall fluid flow between input organic acid 110 and sugaralcohols is properly balanced with the removal of product esters 140 andunreacted sugar alcohols 150 product and elution the effect is toestablish continuous formation of product and continuous chromatographicseparation that can be conducted indefinitely, subject only to the lifeof the column bed.

The process of described herein may also be applied to crude isosorbidereaction mixtures containing unreacted sorbitol. Also, the presentteaching does not involve the use of toxic chemicals, and does notrequire expensive enzymes. Also, a variety of isosorbide esters can beprepared using this process by modifying the choice of organic acidsolvent. For example, a continuous flow of an acetic acid solution ofsorbitol, sorbitan, isosorbide, or a mixture thereof through a solidphase catalyst can result in the formation of mono- and/or di-acetylatedisosorbide. While exemplified herein with acetic acid, the organic acidsuseful for forming cyclic esters may be any branched or straight chainalkanoic acids, substituted and unsubstituted aryl carboxylic acids,alkenoic acids, dicarboxylic acids, fatty acids or mixtures thereof.Typical organic acids of interest include formic acid, acetic,propionic, and butyric acid. Also useful are compound with multiple acidgroups such as diacids like succinic acid, tartaric acid, or fumaricacid and tri-acids like citric acid.

In addition to the above in an entirely different embodiment it has beendiscovered that, exposure of anhydrosugar alcohols to microwaveradiation in the presence of an organic acid and an inorganic acidcatalyst in the liquid phase also provides a method for forming cyclicesters from sugar alcohols and anhydro derivatives thereof. Optionallyan organic solvent that is inert to the reaction conditions may beincluded. In an exemplary embodiment, dioxane is used. Additionalsolvents may include but are not limited to; methyltetrahydrofuran,cyclopentylmethyl ether, alkylated polyether solvents, ketones solventssuch as methyl ethyl ketone, methyl isobutyl ketone and amide solventssuch as dimethyformamide (DMF), dimethylacetamide (DMAC) and N-methylpyrrolidinone (NMP).

The inorganic acid catalyst can be for example, hydrochloric acid,sulfuric acid, phosphoric acid, or hydrofluoric acid. While oxygenatedacids such as sulfuric acid, phosphoric acid are useful for catalyzingthe reaction they may also form cyclic sulfoesters or phosphoesters ofthe sugar alcohol or anhydro derivative thereof as unwanted byproducts.Microwave assisted synthesis of isosorbide esters allows for theenhancement of reaction rates, ease of manipulation, and precise controlover reaction conditions (see Example 3 below). The reaction temperaturefor microwave assisted synthesis of the cyclic esters is typicallybetween 120° C. and 200° C., more typically between 140° C. and 180° C.,and in an exemplary embodiments is about 160° C. These temperatures arehigher than required for synthesis using a solid phase acid catalyst andthe process does not result in a separation of the unreacted productsfrom the diesters. However, the microwave facilitated reaction is lesscostly, faster, and easier to execute. Sugar alcohols, crude mixtures ofsugar alcohols, crude mixtures of anhydrosugar alcohols, includingmonoanhydrosugar and dianhydro derivatives thereof or mixtures thereofmay also be used as a starting source. The process may be performed inbatch or continuously using a pipe, tubing, or similarly constructedflow-through reactor system.

The following examples illustrate specific embodiments of the presentteaching, but are not to be considered as limiting the invention in anymanner.

EXAMPLE 1 Preparation of isosorbide diacetate from sorbitol

Amberlyst 35 resin (50 g) soaked in acetic acid is added to a columnheated to 85° C. The temperature of the column was maintained at 85° C.and a solution of sorbitol (5.00 g) in acetic acid (10 mL) was added.The solution was eluted through the column at a flow rate of 1.2 mL/min.The major product was isosorbide diacetate with the monoacetates alsopresent. The products eluted from the column are summarized in Table 1and depicted in FIG. 1.

TABLE 1 Isosorbide Diacetate Formation using Amberlyst 35 Resin Columnfrom Sorbitol. Frac- Isosorbide tion isosorbide Mono- Isosorbide Sor-Acetic Num- monoacetate acetate Diacetate Isosorbide bi- Acid ber g/kgg/kg g/kg g/kg tol g/kg 1 0.00 0.2 1.14 0.00 963.09 6 4.65 0.31 7.2 3.480.00 923.11 9 10.32 0.92 15.0 10.84 0.00 861.93 12 7.20 0.95 11.9 5.330.00 911.44 15 2.96 0.56 5.0 4.74 0.01 953.86 18 0.91 0.26 1.6 1.82 0.00947.13 21 0.32 0.06 0.4 1.14 0.04 975.11 24 0.0 0.0 0.1 1.80 0.00 977.4234 0.0 0.0 0.0 1.20 0.37 982.22 44 0.0 0.0 0.0 1.17 0.00 975.18

EXAMPLE 2 Preparation of isosorbide diacetate from isosorbide

Amberlyst 35 resin (50 g) soaked in acetic acid is added to a columnheated to 85° C. The temperature of the column was maintained at 85° C.and a solution of isosorbide (5.01 g) in acetic acid (10 mL) was added.The solution was eluted through the column at a flow rate of 1.2 mL/min.The major product was isosorbide diacetate with the monoacetates alsopresent. Table 2 below summarizes the products eluded from the columnwhich are also depicted in FIG. 2.

TABLE 2 Column Elution of Isosorbide through Amberlyst 35 resin packedin Acetic Acid Frac- Isosorbide Sor- tion isosorbide mono- isosorbidebi- Acetic Num- monoacetate acetate diacetate Isosorbide tol Acid ber 1g/kg 2 g/kg g/kg g/kg g/kg g/kg 1 0.07 0.00 0.1 5.76 0.00 964.95 9 0.930.80 1.5 0.00 0.00 965.53 12 9.37 7.62 14.6 9.32 0.00 936.88 15 18.6414.90 35.4 2.57 1.22 890.82 18 21.26 16.65 47.7 7.25 0.00 867.42 2122.76 17.37 58.9 5.66 0.00 840.81 24 18.16 13.49 54.8 3.34 0.00 856.0627 11.40 8.31 37.7 2.39 0.00 896.16 30 5.88 4.04 21.0 1.04 0.00 939.9933 2.55 1.71 9.8 0.15 0.12 961.69 40 0.44 0.29 1.4 1.02 0.00 968.60 460.12 0.06 0.1 1.11 0.00 972.50 54 0.07 0.00 0.1 1.25 0.00 991.09

EXAMPLE 3 Microwave Assisted Synthesis of isosorbide diacetate fromisosorbide

A sample of isosorbide (3 g), acetic acid (30 mL), and 4M HCl in dioxane(1 mL) were placed in a Teflon-lined reaction vessel inside a highdensity rotor for treatment in a MicroSYNTH Microwave Labstation. Thesample was heated from room temperature to 160° C. in 2 min, and kept at160° C. for 20 min using an irradiation power of 1000 Watt. The vesselwas cooled. The final product was composed of 18.9% isosorbide, 14.7%monoester 1, 18.8% monoester 2, and 12.5% diester, which are illustratedin HPLC chromatogram depicted in FIG. 3.

The yields disclosed herein are exemplary only and do not necessarilyreflect the optimal yields possible when reaction conditions areoptimized.

While this invention has been described with reference to severalpreferred embodiments, it is contemplated that various alterations andmodifications thereof will become apparent to those skilled in the artupon a reading of the preceding detailed description. It is thereforeintended that the following appended claims be interpreted as includingall such alterations and modifications as fall within the true spiritand scope of this invention.

1. A method of preparing cyclic esters from 5 or 6 carbon compoundscomprising, contacting a column bed containing a solid acid catalystwith at least one starting 5 or 6 carbon compound selected from thegroup consisting of a sugar alcohol, a monoanhydrosugar alcohol, and adianhydrosugar alcohol in the presence of an organic acid in a singlestep reaction under a single set of reaction conditions for a timesufficient to form at least one of a cyclic monoester and cyclic diesterderivative of at least one of the monoanhydrosugar alcohol and adianhydrosugar alcohol.
 2. The method of claim 1, wherein the bed isconfigured in a simulated moving bed apparatus.
 3. The method of claim1, wherein the organic acid is acetic acid.
 4. The method of claim 1,wherein the starting 5 or 6 carbon compound is selected from groupconsisting of sorbitol, isosorbide and sorbitan.
 5. The method of claim1, wherein the starting 5 or 6 carbon compound is selected from thegroup consisting of arabinitol, ribitol, sorbitol, mannitol, isomannide,galactitol, iditol and xylitol.
 6. The method of claim 1, wherein thesolid acid catalyst is an ion exchange resin.
 7. The method of claim 1,wherein the solid acid catalyst is a zeolite catalyst.
 8. The method ofclaim 6, wherein the solid acid catalyst is selected from the groupconsisting of Amberlyst 35, Amberlyst 15, Amberlyst 36, Amberlyst 70,and Amberlyst 131; Purolite CT-145, Lewatit S2328, Lewatit K2431,Lewatit S2568, Lewatit K2629, SK104, PK228, RCP 160 and Relite RAD/F. 9.The method of claim 6, wherein the solid acid catalyst is Amberlyst 35.10. The method of claim 1, wherein the 5 or 6 carbon starting compoundis recycled back onto the column bed.
 11. The method of claim 1, whereinthe single step reaction under a single set of reaction conditionscomprises an initial reaction temperature selected from the range oftemperatures from 70° to 100° C., and wherein the reaction temperatureremains constant at the initial reaction temperature.
 12. The method ofclaim 1, wherein the single step reaction is conducted in the presenceof water.
 13. The method of claim 1, further comprising: recycling atleast one of a cyclic monoester and cyclic diester derivative of atleast one of the monoanhydrosugar alcohol and a dianhydrosugar alcoholback onto the column bed to form at least one of a cyclic monoester andcyclic diester derivative of at least one of the monoanhydrosugaralcohol and a dianhydrosugar alcohol.